Vitronectin

VTN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1OC0, 1S4G, 1SSU, 2JQ8, 3BT1, 3BT2, 4K24
Identifiers
Aliases	VTN, V75, VN, VNT, vitronectin
External IDs	OMIM: 193190; MGI: 98940; HomoloGene: 532; GeneCards: VTN; OMA:VTN - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q11.2 Start 28,367,284 bp[1] End 28,373,091 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B5|11 46.74 cM Start 78,389,917 bp[2] End 78,393,150 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver right adrenal gland right adrenal cortex left adrenal gland left adrenal cortex gallbladder left ventricle apex of heart placenta right hemisphere of cerebellum Top expressed in neural layer of retina left lobe of liver gallbladder optic nerve retinal pigment epithelium dentate gyrus of hippocampal formation granule cell epithelium of lens sexually immature organism fetal liver hematopoietic progenitor cell pia mater More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding scavenger receptor activity heparin binding extracellular matrix binding polysaccharide binding integrin binding identical protein binding collagen binding extracellular matrix structural constituent Cellular component alphav-beta3 integrin-vitronectin complex extracellular exosome blood microparticle Golgi lumen basement membrane rough endoplasmic reticulum lumen cytoplasm extracellular matrix extracellular space endoplasmic reticulum intracellular membrane-bounded organelle extracellular region collagen-containing extracellular matrix Biological process receptor-mediated endocytosis positive regulation of protein binding cell adhesion positive regulation of cell-substrate adhesion extracellular matrix organization smooth muscle cell-matrix adhesion regulation of complement activation positive regulation of smooth muscle cell migration negative regulation of endopeptidase activity positive regulation of peptidyl-tyrosine phosphorylation positive regulation of vascular endothelial growth factor receptor signaling pathway immune response endodermal cell differentiation positive regulation of wound healing positive regulation of receptor-mediated endocytosis negative regulation of blood coagulation oligodendrocyte differentiation cell adhesion mediated by integrin cell-matrix adhesion protein polymerization liver regeneration cell population proliferation cell migration vesicle-mediated transport endocytosis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7448 22370 Ensembl ENSG00000109072 ENSMUSG00000017344 UniProt P04004 P29788 RefSeq (mRNA) NM_000638 NM_011707 RefSeq (protein) NP_000629 NP_035837 Location (UCSC) Chr 17: 28.37 – 28.37 Mb Chr 11: 78.39 – 78.39 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is synthesized and excreted by the liver, and abundantly found in serum, the extracellular matrix and bone.^[5] In humans it is encoded by the VTN gene.^[6][7]

Vitronectin binds to integrin alpha-V beta-3 and thus promotes cell adhesion and spreading. It also inhibits the membrane-damaging effect of the terminal cytolytic complement pathway and binds to several serpins (serine protease inhibitors). It is a secreted protein and exists in either a single chain form or a clipped, two chain form held together by a disulfide bond.^[6] Vitronectin has been speculated to be involved in hemostasis^[8] and tumor malignancy.^[9][10]

Vitronectin is a 54 kDa glycoprotein, consisting of 478 amino acid residues. About one-third of the protein's molecular mass is composed of carbohydrates. On occasion, the protein is cleaved after arginine 379, to produce two-chain vitronectin, where the two parts are linked by a disulfide bond. No high-resolution structure has been determined experimentally yet, except for the N-terminal domain.

The protein consists of three domains:

• The N-terminal Somatomedin B domain (1-39)
• A central domains with hemopexin homology (131-342)
• A C-terminal domain (residues 347-459) also with hemopexin homology.

Several structures has been reported for the Somatomedin B domain. The protein was initially crystallized in complex with one of its physiological binding partners: the Plasminogen activator inhibitor-1 (PAI-1) and the structure solved for this complex.^[11] Subsequently two groups reported NMR structures of the domain.^[12][13]

The somatomedin B domain is a close-knit disulfide knot, with 4 disulfide bonds within 35 residues. Different disulfide configurations had been reported for this domain^[14][15][16] but this ambiguity has been resolved by the crystal structure.^[16]

Homology models have been built for the central and C-terminal domains.^[16]

The somatomedin B domain of vitronectin binds to plasminogen activator inhibitor-1 (PAI-1), and stabilizes it.^[11] Thus vitronectin serves to regulate proteolysis initiated by plasminogen activation. In addition, vitronectin is a component of platelets and is, thus, involved in hemostasis. Vitronectin contains an RGD (45-47) sequence, which is a binding site for membrane-bound integrins, e.g., the vitronectin receptor, which serve to anchor cells to the extracellular matrix. The Somatomedin B domain interacts with the urokinase receptor, and this interaction has been implicated in cell migration and signal transduction. High plasma levels of both PAI-1 and the urokinase receptor have been shown to correlate with a negative prognosis for cancer patients. Cell adhesion and migration are directly involved in cancer metastasis, which provides a probable mechanistic explanation for this observation.

• Vitronectin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)